Is the pharmaceutical sector prepared to face a titanium dioxide ban?

Dr Subhashis Chakraborty, head of Global Product Management, ACG Capsules

In the wake of the ban on titanium dioxide (TiO₂) E171 in the production of food and dietary supplements in the EU, the pharmaceutical industry may face a similar ban as early as 2025.

Why exactly is titanium dioxide’s safety being questioned? If its safety is really a concern, is there a possibility of phasing it out completely from the EU? How prepared is the industry to cope with this change? Won’t this decision affect other global markets? What position have other regulatory authorities already taken? What could be the potential implication of this ban across other geographies? These are just a few of the major questions that remain unanswered and a key concern for the pharmaceutical industry.

Considering Europe as an important reference market, although the ban is applicable to the European jurisdiction, its restricted use or complete prohibition in the production of drug products by the European Medicine Agency (EMA) may soon result in a snowball effect on other global markets. Moreover, companies supplying medicines to the EU and other regions will find themselves having to handle two parallel versions of every product – one containing TiO₂ and another devoid of it. More importantly, imagine the scenario of the drug shortage that could arise if appropriate alternatives are not identified, or they become inadequately available.

TiO₂ has been used as a colouring and opacifying agent in the pharmaceutical industry for more than half a century. From capsule shells, tablet and pellet coatings, to suspensions and pastes, it is almost ubiquitously used in a wide range of dosage forms to impart product aesthetics and protect sensitive APIs from degradation. Unfortunately, no other excipient has been able to demonstrate a similar whiteness and opacity to TiO₂. Therefore, although there are possibilities, replacements will have certain limitations. New formulation development may not be challenging but finding alternatives for more than 90,000 existing marketed products will take a heavy toll from a financial, time and resource point of view. This could be coupled with the myriad uncertainties of drug products being withdrawn from the market impacting the health of millions.

There is already diverse opinion in the scientific community. Many global regulators in geographies such as Canada, UK, Australia/New Zealand and the United States have already taken an independent stance to disagree with the precautionary measures taken in the EU. Reformulating the existing drug products is not as simple as it appears. Replacement of TiO₂ with an alternative is a mammoth task as it requires assessment from different aspects including regulations, compatibility, safety, efficacy, processibility and stability. While the International Pharmaceutical Excipients Council (IPEC) along with the members of the Innovation & Quality (IQ) Consortium are working to explore the appropriate strategy to handle the situation, pharmaceutical companies are looking out for TiO₂ alternatives for their new developments.

The allied industry supporting the pharmaceutical sector has started offering alternative excipients like calcium carbonate, talc and starch for white options and iron oxides for colored options. Whichever has worked best to support their ecosystem is related to either a coating mixture or an empty hard capsule shell. At ACG Capsules, we sensed the looming issue some time ago and – irrespective of the fate of the TiO₂ ban in the industry – have partnered with the industry to support them by offering the right available alternatives under the brand of ACGcaps TSafe – including different colored variants in both gelatin and cellulose-based capsules. Additionally, we have worked with the companies on technical training – focusing on educational aspects around the alternatives.  

At this stage, there are no answers. With so many unforeseen obstacles along the way, it is difficult to predict whether TiO₂ will be banned in pharma. Its fate would depend on how the scientific data and rationale being generated takes shape and, on the other hand, how it will be perceived by the regulatory bodies. For now, the only option available for the excipient manufacturers is to support and work closely with the formulators, in order to ensure the industry can correctly progress and to be prepared to face the outcomes of a TiO₂ ban.

 

 

 

 

 

 

 

 

 

 

Source: https://pharmafile.com/